Details
| Stereochemistry | MIXED |
| Molecular Formula | 2C19H15O4.C3H8O.2Na |
| Molecular Weight | 720.7146 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 0 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].CC(C)O.CC(=O)CC(C1=CC=CC=C1)C2=C([O-])C3=CC=CC=C3OC2=O.CC(=O)CC(C4=CC=CC=C4)C5=C([O-])C6=CC=CC=C6OC5=O
InChI
InChIKey=VLYIGFRRLKDPQS-UHFFFAOYSA-L
InChI=1S/2C19H16O4.C3H8O.2Na/c2*1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22;1-3(2)4;;/h2*2-10,15,21H,11H2,1H3;3-4H,1-2H3;;/q;;;2*+1/p-2
Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Warfarin is marketed under the brand name Coumadin among others. Coumadin (crystalline warfarin sodium) is an anticoagulant which acts by inhibiting vitamin
K-dependent coagulation factors. Chemically, it is 3-(α-acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the R- and S-enantiomers. Coumadin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. It is also indicated for the prophylaxis and/or treatment of the thromboembolic
complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. The degree of depression is dependent upon the dosage
administered and, in part, by the patient’s VKORC1 genotype. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 24.7 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
|||
| Preventing | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
|||
| Preventing | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2186 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
52278 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
32.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7 day |
single, oral |
WARFARIN unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1% |
single, oral |
WARFARIN unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
Disc. AE: Vomiting, Loss of consciousness... AEs leading to discontinuation/dose reduction: Vomiting Sources: Page: p.718Loss of consciousness |
150 mg single, oral Overdose Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: chlorpromazine, p.o(3 g, single) Sources: Page: p.718 |
unhealthy, 44 n = 1 Health Status: unhealthy Condition: Aortic valve replacement Age Group: 44 Sex: M Population Size: 1 Sources: Page: p.718 |
Disc. AE: Drowsiness... AEs leading to discontinuation/dose reduction: Drowsiness Sources: Page: p.718 |
540 mg single, oral Overdose Dose: 540 mg Route: oral Route: single Dose: 540 mg Co-administed with:: clonazepam, p.o(4 mg, single) Sources: Page: p.1 |
healthy, 59 n = 1 Health Status: healthy Age Group: 59 Sex: F Population Size: 1 Sources: Page: p.1 |
|
5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Disc. AE: Hemoptysis, Hematuria... AEs leading to discontinuation/dose reduction: Hemoptysis Sources: Page: p.1Hematuria Dyspnea Cough |
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction Sources: Page: p.1 |
Disc. AE: Bleeding... AEs leading to discontinuation/dose reduction: Bleeding (grade 5) Sources: Page: p.1 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Loss of consciousness | Disc. AE | 125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
| Vomiting | Disc. AE | 125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
| Drowsiness | Disc. AE | 150 mg single, oral Overdose Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: chlorpromazine, p.o(3 g, single) Sources: Page: p.718 |
unhealthy, 44 n = 1 Health Status: unhealthy Condition: Aortic valve replacement Age Group: 44 Sex: M Population Size: 1 Sources: Page: p.718 |
| Cough | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
| Dyspnea | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
| Hematuria | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
| Hemoptysis | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
| Bleeding | grade 5 Disc. AE |
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction Sources: Page: p.1 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes [Ki 8 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes | ||||
| yes | ||||
| yes | ||||
| yes | likely (co-administration study) Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
|||
| yes | likely (co-administration study) Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
|||
| yes | yes (pharmacogenomic study) Comment: If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants; Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Chondrodysplasia punctata and maternal warfarin use during pregnancy. | 1975 Mar |
|
| Central retinal vein occlusion associated with primary pulmonary hypertension. | 2001 |
|
| Abdominal wall hematoma as a complication of warfarinization. | 2001 Apr |
|
| Spontaneous subcapsular renal hematoma secondary to anticoagulant therapy. | 2001 Apr |
|
| Behçet's disease with a large intracardiac thrombus: a case report. | 2001 Apr |
|
| Perioperative management and reversal of antithrombotic therapy. | 2001 Feb |
|
| Thrombolysis and antithrombotic therapy for coronary artery disease. | 2001 Feb |
|
| Antithrombotic therapy in valvular heart disease. | 2001 Feb |
|
| Oral anticoagulants. Pharmacologic issues for use in the elderly. | 2001 Feb |
|
| Anticoagulation and cataract surgery: a review of the current literature. | 2001 Feb |
|
| [Incidence of tumors after treatment with oral anticoagulants]. | 2001 Feb |
|
| Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis. | 2001 Feb |
|
| Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous administration to healthy volunteers. | 2001 Feb 15 |
|
| Central venous device-related infection and thrombosis in patients treated with moderate dose continuous-infusion interleukin-2. | 2001 Feb 15 |
|
| What is the best emergency treatment for children who ingest warfarin rodenticide? | 2001 Feb 5 |
|
| [Old adrenal hematoma: a case report]. | 2001 Jan |
|
| Regarding postoperative stroke after warfarin for cutaneous surgery. | 2001 Jan |
|
| Catastrophic antiphospholipid antibody syndrome. | 2001 Jan |
|
| Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. | 2001 Jan |
|
| Need for increased dose of warfarin in HIV patients taking nevirapine. | 2001 Jan 26 |
|
| Acute spontaneous haematoma of the rectum. | 2001 Jan-Feb |
|
| Sneddon's syndrome: a case report. | 2001 Mar |
|
| Perception of teratogenic risk of common medicines. | 2001 Mar |
|
| Long-term results of venous revascularization for Paget-Schroetter syndrome in athletes. | 2001 Mar |
|
| Prevention, diagnosis, and treatment of venous thromboembolic complications of gynecologic surgery. | 2001 Mar |
|
| Increase in international normalized ratio associated with smoking cessation. | 2001 Mar |
|
| The association of vitamin K status with warfarin sensitivity at the onset of treatment. | 2001 Mar |
|
| A case report of warfarin resistance due to azathioprine and review of the literature. | 2001 Mar |
|
| Evaluation of very low-dose subcutaneous vitamin K during postoperative warfarin therapy. | 2001 Mar |
|
| Palliative care for the elderly. | 2001 Mar |
|
| Treatment of the patient with deep vein thrombosis. | 2001 Mar |
|
| Aspirin does not influence the effect of angiotensin-converting enzyme inhibition on left ventricular ejection fraction 3 months after acute myocardial infarction. | 2001 Mar |
|
| Hemoptysis in patients with renal insufficiency : the role of flexible bronchoscopy. | 2001 Mar |
|
| Efficacy and safety of intravenous phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. | 2001 Mar |
|
| Improving medication safety across a multihospital system. | 2001 Mar |
|
| Potential clinical efficacy and cost benefit of a transesophageal echocardiography-guided low-molecular-weight heparin (enoxaparin) approach to antithrombotic therapy in patients undergoing immediate cardioversion from atrial fibrillation. | 2001 Mar |
|
| Atrial fibrillation and stroke : concepts and controversies. | 2001 Mar |
|
| Low-dose warfarin fails to prolong survival of dual lumen venous dialysis catheters. | 2001 Mar |
|
| Mutations of the CYP2C9 gene and the response to warfarin. | 2001 Mar |
|
| Antiphospholipid antibody syndrome and renal disease. | 2001 Mar |
|
| When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment. | 2001 Mar |
|
| Management of thrombosis in women with antiphospholipid syndrome. | 2001 Mar |
|
| Mild head injury, anticoagulants, and risk of intracranial injury. | 2001 Mar 10 |
|
| Dalteparin vs warfarin in hip arthroplasty patients. | 2001 Mar 12 |
|
| Profile of moxifloxacin drug interactions. | 2001 Mar 15 |
|
| Subarachnoid haemorrhage. | 2001 Mar 17 |
|
| Warfarin therapy for an octogenarian who has atrial fibrillation. | 2001 Mar 20 |
|
| Vitamin K for warfarin-associated coagulopathy. | 2001 Mar 3 |
|
| Clinical trials that have influenced the treatment of venous thromboembolism: a historical perspective. | 2001 Mar 6 |
|
| What is the optimal medical management of ischemic heart failure? | 2001 Mar-Apr |
Patents
Sample Use Guides
Usual Adult Dose for Prevention of Thromboembolism in Atrial Fibrillation Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Usual Adult Dose for Myocardial Infarction
Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Usual Adult Dose for Deep Vein Thrombosis - Prophylaxis
Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Route of Administration:
Oral
In Vitro Use Guide
Curator's Comment: One strain (TAS) is susceptible and two strains (HW and HS) resistant to the anticoagulant and lethal effects of warfarin.
Vitamin K-reductase activity was inhibited by approximately 13 and 8% respectively when microsomal preparations from TAS and HW animals were incubated with 50 uM vitamin K1 and 10 uM warfarin.
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4V2UBU7H8W
Created by
admin on Fri Dec 15 14:59:39 GMT 2023 , Edited by admin on Fri Dec 15 14:59:39 GMT 2023
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145996738
Created by
admin on Fri Dec 15 14:59:39 GMT 2023 , Edited by admin on Fri Dec 15 14:59:39 GMT 2023
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
